Research Plan Summary/Abstract The Michigan PBB Cohort is the longest running, multi-generational cohort study of a widespread environmental contamination event in the United States. More than 40 years ago, millions of Michiganders ate farm products contaminated with polybrominated biphenyls (PBB), a chemical flame retardant. This cohort of approximately 7,500 individuals includes those who ate the contaminated food, chemical plant workers, their children, and their grandchildren. Extensive health, exposure, and biological samples have been collected from these individuals for four decades. While systematic updates of this cohort ceased in 2003 due to paucity of infrastructure funds, the Emory team pursued hypothesis-driven research with NIH funding. Research based on the Michigan PBB Cohort has demonstrated relationships between exposure to PBB and many health outcomes, including thyroid conditions, breast cancer risk, lower Apgar scores in children, reproductive health in daughters, and genitourinary abnormalities in sons. Current NIH-funded research includes innovative approaches involving genomics, epigenomics, exposomics and metabolomics across multiple generations as well as a randomized clinical trial of a nutritional aid hypothesized to speed elimination of PBB. The PBB research team has been exceedingly productive, contributing over 150 scientific communications. The PBB cohort has served as a source of data and biospecimens for eight NIH R01 grants, two EPA STAR grants, an NIH R03, and an NIH R21, reflecting the important scientific questions that can be addressed with this cohort. Importantly, for the last 6 years, the affected Michigan community has become a partner in the PBB research efforts, dedicating their time and resources to support the continuation of this work that is so meaningful to their family's and community's health. To assure this valuable cohort is accessible and useful for future studies and data sharing, with this R24 support we plan to update the vital status of the entire cohort and to develop a state-of-the-art data management and analytic platform. This platform will enable linkage of over 40 years of follow-up data and thousands of biospecimens. Using state of the art web-based communication, we will develop web portals to enable broad sharing of the cohort resources with three important stakeholder groups: the scientific community, cohort members (to access their own data), and local public health agencies. This infrastructure grant will support research addressing the long-term impact of exposure to brominated flame retardants, which continues to be found in the blood of the vast majority of Americans - making the intensive study of this unique cohort relevant to all Americans.